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https://www.readbyqxmd.com/read/27890916/polydatin-ameliorates-staphylococcus-aureus-induced-mastitis-in-mice-via-inhibiting-tlr2-mediated-activation-of-the-p38-mapk-nf-%C3%AE%C2%BAb-pathway
#1
Kang-Feng Jiang, Gan Zhao, Gan-Zhen Deng, Hai-Chong Wu, Nan-Nan Yin, Xiu-Ying Chen, Chang-Wei Qiu, Xiu-Li Peng
Recent studies show that Polydatin (PD) extracted from the roots of Polygonum cuspidatum Sieb, a widely used traditional Chinese remedies, possesses anti-inflammatory activity in several experimental models. In this study, we investigated the anti-inflammatory effects of PD on Staphylococcus aureus-induced mastitis in mice and elucidated the potential mechanisms. In mice with S aureus-induced mastitis, administration of PD (15, 30, 45 mg/kg, ip) or dexamethasone (Dex, 5 mg/kg, ip) significantly suppressed the infiltration of inflammatory cells, ameliorated the mammary structural damage, and inhibited the activity of myeloperoxidase, a biomarker of neutrophils accumulation...
November 28, 2016: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/27883089/hydrogen-sulfide-and-or-ammonia-reduces-spermatozoa-motility-through-ampk-akt-related-pathways
#2
Yong Zhao, Wei-Dong Zhang, Xin-Qi Liu, Peng-Fei Zhang, Ya-Nan Hao, Lan Li, Liang Chen, Wei Shen, Xiang-Fang Tang, Ling-Jiang Min, Qing-Shi Meng, Shu-Kun Wang, Bao Yi, Hong-Fu Zhang
A number of emerging studies suggest that air pollutants such as hydrogen sulfide (H2S) and ammonia (NH3) may cause a decline in spermatozoa motility. The impact and underlying mechanisms are currently unknown. Boar spermatozoa (in vitro) and peripubertal male mice (in vivo) were exposed to H2S and/or NH3 to evaluate the impact on spermatozoa motility. Na2S and/or NH4Cl reduced the motility of boar spermatozoa in vitro. Na2S and/or NH4Cl disrupted multiple signaling pathways including decreasing Na(+)/K(+) ATPase activity and protein kinase B (AKT) levels, activating Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) and phosphatase and tensin homolog deleted on chromosome ten (PTEN), and increasing reactive oxygen species (ROS) to diminish boar spermatozoa motility...
November 24, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27872270/hiv-glycoprotein-gp120-impairs-fast-axonal-transport-by-activating-tak1-signaling-pathways
#3
Sarah H Berth, Nichole Mesnard-Hoaglin, Bin Wang, Hajwa Kim, Yuyu Song, Maria Sapar, Gerardo Morfini, Scott T Brady
Sensory neuropathies are the most common neurological complication of HIV. Of these, distal sensory polyneuropathy (DSP) is directly caused by HIV infection and characterized by length-dependent axonal degeneration of dorsal root ganglion (DRG) neurons. Mechanisms for axonal degeneration in DSP remain unclear, but recent experiments revealed that the HIV glycoprotein gp120 is internalized and localized within axons of DRG neurons. Based on these findings, we investigated whether intra-axonal gp120 might impair fast axonal transport (FAT), a cellular process critical for appropriate maintenance of the axonal compartment...
December 2016: ASN Neuro
https://www.readbyqxmd.com/read/27863449/il6-mediated-inflammatory-loop-reprograms-normal-to-emt-metastatic-cscs-in-pre-neoplastic-liver-of-tgf%C3%AE-deficient-%C3%AE-2sp-mice
#4
Abhisek Mitra, Jun Yan, Xueqing Xia, Shouhao Zhou, Jian Chen, Lopa Mishra, Shulin Li
Hepatocellular carcinoma (HCC) is the second-leading cause of cancer-related deaths world-wide with poor survival rate. As many as 40% of HCCs are clonal, with alteration of key tumor suppressor pathways in stem cells is the primary cause of HCC initiation. However, mechanisms that generate metastatic stem cells in pre-neoplastic liver tissue are not well understood. We hypothesized that chronic inflammation is a major driver of the transformation of genetically defective liver stem cells (LSCs) into highly metastatic liver cancer cells in premalignant liver tissue...
November 18, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/27847434/novel-functional-roles-of-caspase-related-genes-in-the-regulation-of-apoptosis-and-autophagy
#5
Ju-Hyun Shin, Sang-Hyun Min
Caspases, a family of cysteine proteases, cleave substrates and play significant roles in apoptosis, autophagy, and development. Recently, our group identified 72 genes that interact with Death Caspase-1 (DCP-1) proteins in Drosophila by genetic screening of 15,000 EP lines. However, the cellular functions and molecular mechanisms of the screened genes, such as their involvement in apoptosis and autophagy, are poorly understood in mammalian cells. In order to study the functional characterizations of the genes in human cells, we investigated 16 full-length human genes in mammalian expression vectors and tested their effects on apoptosis and autophagy in human cell lines...
November 2016: Korean Journal of Physiology & Pharmacology
https://www.readbyqxmd.com/read/27847407/anti-inflammatory-effects-of-traf-interacting-protein-in-rheumatoid-arthritis-fibroblast-like-synoviocytes
#6
Qing-Zhu Kong, Li-Tao Guo, Jia-Ning Yang, Yan-Fei Wang, Jing-Xin Zhao, Su-Hong Kong, Meng Zhang, Shi Yan, Yu Jin
Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease characterized by inflammatory cell infiltration, synovial inflammation, and cartilage destruction. Proliferative fibroblast-like synoviocytes (FLS) play crucial roles in both propagation of inflammation and joint damage because of their production of great amount of proinflammatory cytokines and proteolytic enzymes. In this study, we investigate the role of TRAF-interacting protein (TRIP) in regulating inflammatory process in RA-FLS. TRIP expression was attenuated in RA-FLS compared with osteoarthritis- (OA-) FLS...
2016: Mediators of Inflammation
https://www.readbyqxmd.com/read/27834881/salidroside-regulates-inflammatory-response-in-raw-264-7-macrophages-via-tlr4-tak1-and-ameliorates-inflammation-in-alcohol-binge-drinking-induced-liver-injury
#7
Peng Sun, Shun-Zong Song, Shuang Jiang, Xia Li, You-Li Yao, Yan-Ling Wu, Li-Hua Lian, Ji-Xing Nan
The current study was designed to investigate the anti-inflammatory effect of salidroside (SDS) and the underlying mechanism by using lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages in vitro and a mouse model of binge drinking-induced liver injury in vivo. SDS downregulated protein expression of toll-like receptor 4 (TLR4) and CD14. SDS inhibited LPS-triggered phosphorylation of LPS-activated kinase 1 (TAK1), p38, c-Jun terminal kinase (JNK), and extracellular signal-regulated kinase (ERK). Degradation of IκB-α and nuclear translocation of nuclear factor (NF)-κB were effectively blocked by SDS...
November 9, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/27821647/preclinical-evaluation-of-drugs-to-block-inflammation-driven-preterm-birth
#8
Demelza J Ireland, Elizabeth A Nathan, Shaofu Li, Adrian K Charles, Lisa F Stinson, Matthew W Kemp, John P Newnham, Jeffrey A Keelan
Intrauterine inflammation, the major cause of early preterm birth, can have microbial and sterile aetiologies. We assessed in a Transwell model the anti-inflammatory efficacies of five drugs on human extraplacental membranes delivered after preterm spontaneous labour (30-34 wk). Drugs [TPCA1 (IKKβ inhibitor), 5 z-7-oxozeaenol (OxZ, TAK1 inhibitor), inhibitor of NF-κB essential modulator binding domain (iNBD), SB239063 (p38 MAPK inhibitor) and N-acetyl cysteine (free radical scavenger free radicals)] were added after 12 h equilibration to the amniotic compartment...
November 7, 2016: Innate Immunity
https://www.readbyqxmd.com/read/27820799/profiling-drugs-for-rheumatoid-arthritis-that-inhibit-synovial-fibroblast-activation
#9
Douglas S Jones, Anne P Jenney, Jennifer L Swantek, John M Burke, Douglas A Lauffenburger, Peter K Sorger
Activation of synovial fibroblasts (SFs) contributes to rheumatoid arthritis (RA) by damaging synovial membranes and generating inflammatory cytokines that recruit immune cells to the joint. In this paper we profile cytokine secretion by primary human SFs from healthy tissues and from donors with RA and show that SF activation by TNF, IL-1α, and polyinosinic-polycytidylic acid (Poly(I:C)) cause secretion of multiple cytokines found at high levels in RA synovial fluids. We used interaction multiple linear regression to quantify therapeutic and countertherapeutic drug effects across activators and donors and found that the ability of drugs to block SF activation was strongly dependent on the identity of the activating cytokine...
October 31, 2016: Nature Chemical Biology
https://www.readbyqxmd.com/read/27803473/development-of-a-method-for-converting-a-tak1-type-i-inhibitor-into-a-type-ii-or-c-helix-out-inhibitor-by-structure-based-drug-design-sbdd
#10
Terushige Muraoka, Mitsuaki Ide, Machiko Irie, Kenji Morikami, Takaaki Miura, Masamichi Nishihara, Hirotaka Kashiwagi
We have developed a method for converting a transforming growth factor-β-activated kinase 1 (TAK1) type I inhibitor into a type II or c-helix-out inhibitor by structure-based drug design (SBDD) to achieve an effective strategy for developing these different types of kinase inhibitor in parallel. TAK1 plays a key role in inflammatory and immune signaling, and is therefore considered to be an attractive molecular target for the treatment of human diseases (inflammatory disease, cancer, etc.). We have already reported novel type I TAK1 inhibitor, so we utilized its X-ray information to design a new chemical class type II and c-helix-out inhibitors...
2016: Chemical & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/27793515/corrigendum-to-modification-of-tak1-by-o-linked-n-acetylglucosamine-facilitates-tak1-activation-and-promotes-m1-macrophage-polarization-cell-signal-28-11-2016-1742-1752
#11
Dongmei Zhang, Zhiwei Xu, Tao Tao, Xiaojuan Liu, Xiaolei Sun, Yuhong Ji, Lijian Han, Huiyuan Qiu, Guizhou Zhu, Yifen Shen, Liang Zhu, Aiguo Shen
No abstract text is available yet for this article.
October 26, 2016: Cellular Signalling
https://www.readbyqxmd.com/read/27791197/epigallocatechin-3-gallate-egcg-suppresses-melanoma-cell-growth-and-metastasis-by-targeting-traf6-activity
#12
Jianglin Zhang, Zhou Lei, Zunnan Huang, Xu Zhang, Youyou Zhou, Zhongling Luo, Weiqi Zeng, Juan Su, Cong Peng, Xiang Chen
TRAF6 (TNF Receptor-Associated Factor 6) is an E3 ubiquitin ligase that contains a Ring domain, induces K63-linked polyubiquitination, and plays a critical role in signaling transduction. Our previous results demonstrated that TRAF6 is overexpressed in melanoma and that TRAF6 knockdown dramatically attenuates tumor cell growth and metastasis. In this study, we found that EGCG can directly bind to TRAF6, and a computational model of the interaction between EGCG and TRAF6 revealed that EGCG probably interacts with TRAF6 at the residues of Gln54, Gly55, Asp57 ILe72, Cys73 and Lys96...
October 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/27789770/a-pilot-study-examining-the-impact-of-exercise-training-on-skeletal-muscle-genes-related-to-the-tlr-signaling-pathway-in-older-adults-following-hip-fracture
#13
Alec I McKenzie, Robert A Briggs, Katherine M Barrows, Daniel S Nelson, Oh Sung Kwon, Paul N Hopkins, Thomas F Higgins, Robin L Marcus, Micah J Drummond
Older adults after hip fracture surgery experience progressive muscle atrophy and weakness limiting full recovery. Further understanding of the molecular mechanisms in muscle with adaptation to exercise training in this vulnerable population is necessary. Therefore, we conducted a pilot study to investigate the skeletal muscle inflammatory and ceramide biosynthesis gene expression levels associated with the toll-like receptor (TLR) pathway before (Pre) and following a 3-month multi-component exercise training program in older adults (3M, 4F; 78...
October 27, 2016: Journal of Applied Physiology
https://www.readbyqxmd.com/read/27768832/articular-cartilage-injury-rapidly-activates-tak1-in-chondrocytes-by-inducing-its-phosphorylation-and-k63-polyubiquitination
#14
Heba M Ismail, Athanasios Didangelos, Tonia L Vincent, Jeremy Saklatvala
Objectives Mechanical injury to cartilage predisposes to osteoarthritis (OA). Wounding the articular cartilage surface causes rapid activation of MAP kinases and NFκB mimicking the response to inflammatory cytokines. Here, we identify the upstream signalling mechanisms involved. Methods Cartilage was injured by dissecting it from the articular surface of porcine metacarpophalangeal joints (MCP) or by avulsing murine proximal femoral epiphyses. Protein phosphorylation was assayed by Western blotting of cartilage lysates...
October 21, 2016: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/27764753/inactivation-of-transforming-growth-factor-%C3%AE-activated-kinase-1-promotes-taxol-efficacy-in-ovarian-cancer-cells
#15
Li Bo, Huchuan Cui, Zhengxian Fang, Tao Qun, Caoyun Xia
Resistance to taxol represents a major obstacle for long-term remission in ovarian cancer. Transforming Growth Factor-β-Activated Kinase 1 (TAK1) is a critical component in immune response pathway. However, the role of TAK1 in the development of chemoresistance in ovarian cancer remains unknown. Here, we showed that in vitro, taxol-resistant cells expressed higher TAK1, and the ratio of p-TAK1/TAK1 positively associated with taxol resistance in ovarian cancer cells. Inactivation of TAK1 by inhibitor 5Z-7-oxozeaenol or gene knockdown sensitized taxol cytotoxicity in vitro, promoting cell apoptosis and mitosis arrest...
October 17, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27733681/vitamin-b6-prevents-il-1%C3%AE-production-by-inhibiting-nlrp3-inflammasome-activation
#16
Peipei Zhang, Kohsuke Tsuchiya, Takeshi Kinoshita, Hiroko Kushiyama, Sofya Suidasari, Mizuki Hatakeyama, Hisanori Imura, Norihisa Kato, Takashi Suda
Vitamin B6 includes six water-soluble vitamers: pyridoxal (PL), pyridoxamine (PM), pyridoxine (PN), and their phosphorylated forms. Pyridoxal 5'-phosphate (PLP) is an important cofactor for many metabolic enzymes. Several lines of evidence demonstrate that blood levels of PLP are significantly lower in patients with inflammation than in control subjects, and that vitamin B6 has anti-inflammatory effects, with therapeutic potential for a variety of inflammatory diseases. Although one of our group (NK) previously demonstrated that PL inhibits the NF-κB pathway, the molecular mechanism by which vitamin B6 suppresses inflammation is not well understood...
October 12, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27732951/ikk-nf-%C3%AE%C2%BAb-signaling-contributes-to-glioblastoma-stem-cell-maintenance
#17
Amanda L Rinkenbaugh, Patricia C Cogswell, Barbara Calamini, Denise E Dunn, Anders I Persson, William A Weiss, Donald C Lo, Albert S Baldwin
Glioblastoma multiforme (GBM) carries a poor prognosis and continues to lack effective treatments. Glioblastoma stem cells (GSCs) drive tumor formation, invasion, and drug resistance and, as such, are the focus of studies to identify new therapies for disease control. Here, we identify the involvement of IKK and NF-κB signaling in the maintenance of GSCs. Inhibition of this pathway impairs self-renewal as analyzed in tumorsphere formation and GBM expansion as analyzed in brain slice culture. Interestingly, both the canonical and non-canonical branches of the NF-κB pathway are shown to contribute to this phenotype...
October 6, 2016: Oncotarget
https://www.readbyqxmd.com/read/27723266/effects-of-tgf-%C3%AE-1-on-plasminogen-activation-in-human-dental-pulp-cells-role-of-alk5-smad2-tak1-and-mek-erk-signaling
#18
Mei-Chi Chang, Hsiao-Hua Chang, Po-Shuan Lin, Yu-An Huang, Chiu-Po Chan, Yi-Ling Tsai, Shen-Yang Lee, Po-Yuan Jeng, Han-Yueh Kuo, Sin-Yuet Yeung, Jiiang-Huei Jeng
Transforming growth factor-β1 (TGF-β1) plays an important role in the pulpal repair and dentinogenesis. Plasminogen activation (PA) system regulates extracellular matrix turnover. In this study, we investigated the effects of TGF-β1 on PA system of dental pulp cells and its signaling pathways. Dental pulp cells were treated with different concentrations of TGF-β1. MTT assay, reverse transcription-polymerase chain reaction (RT-PCR), western blotting and enzyme-linked immunosorbant assay (ELISA) were used to detect the effect of TGF-β1 on cell viability, mRNA and protein expression of urokinase-type plasminogen activator (uPA), uPA receptor (uPAR), plasminogen activator inhibitor-1 (PAI-1) as well as their secretion...
October 9, 2016: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/27713136/the-role-of-extracellular-vesicles-in-mediating-progression-metastasis-and-potential-treatment-of-hepatocellular-carcinoma
#19
Naibin Yang, Shanshan Li, Guoxiang Li, Shengguo Zhang, Xinyue Tang, Shunlan Ni, Xiaomin Jian, Cunlai Xu, Jiayin Zhu, Mingqin Lu
Hepatocellular carcinoma (HCC) is a major cause of cancer-related death worldwide. As vectors for intercellular information exchange, the potential role of extracellular vesicles (EVs) in HCC formation, progression and therapy has been widely investigated. In this review, we explore the current status of the researches in this field. Altogether there is undeniable evidence that EVs play a crucial role in HCC development, metastasis. Moreover, EVs have shown great potential as drug delivery systems (DDSs) for the treatment of HCC...
October 4, 2016: Oncotarget
https://www.readbyqxmd.com/read/27699262/increased-apoptosis-and-browning-of-tak1-deficient-adipocytes-protects-against-obesity
#20
Antonia Sassmann-Schweda, Pratibha Singh, Cong Tang, Astrid Wietelmann, Nina Wettschureck, Stefan Offermanns
Obesity is an increasing health problem worldwide, and nonsurgical strategies to treat obesity have remained rather inefficient. We here show that acute loss of TGF-β-activated kinase 1 (TAK1) in adipocytes results in an increased rate of apoptotic adipocyte death and increased numbers of M2 macrophages in white adipose tissue. Mice with adipocyte-specific TAK1 deficiency have reduced adipocyte numbers and are resistant to obesity induced by a high-fat diet or leptin deficiency. In addition, adipocyte-specific TAK1-deficient mice under a high-fat diet showed increased energy expenditure, which was accompanied by enhanced expression of the uncoupling protein UCP1...
May 19, 2016: JCI Insight
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